Serum cholesterol and serum triglyceride levels are important factors in the development of cardiovascular disease. In many clinical studies there is a positive correlation between plasma triglycerides and the incidence of cardiovascular disease [1]. Elevated plasma triglyceride level is frequently associated with other atherogenic factors including elevated low-density lipoprotein (LDL)-cholesterol, reduced high-density lipoprotein (HDL)-cholesterol, and small LDL particles [2, 3]. There is growing acceptance that triglycerides act in a synergistic fashion with these other lipid risk factors to increase the incidence of cardiovascular disease [4, 5]. Hypertriglyceridemia usually occurs because of insulin resistance, which leads to overproduction of very low-density lipoproteins (VLDL) by the liver [3]. Treatment involves lifestyle changes to decrease body weight and to increase physical activity, both of which improve insulin sensitivity. Drug therapy to lower triglycerides involves the use of fibrates or nicotinic acid [6].
A number of clinical studies convincingly establish plasma cholesterol and LDL-cholesterol as independent risk factors for coronary heart disease [7]. Pharmacological agents, called statins, lower total plasma cholesterol by inhibiting the synthesis of cholesterol by the liver. The statins reduce the morbidity and mortality rate from cardiovascular disease in high risk, hypercholesterolemic patients [8, 9], but also in persons who exhibit “average” cholesterol levels [10]. Another approach is to interfere with the intestinal absorption of cholesterol. Certain phytosterols (plant sterols) such as stigmasterol and β-sitosterol lower serum cholesterol act by inhibiting absorption of both dietary and biliary cholesterol from the small intestine [11].
With respect to the most appropriate form of phytosterols for lowering serum cholesterol, some reports indicate that free phytosterols reduce serum cholesterol in animals and humans [12, 13]. However, there is also evidence to indicate that a sterol esterified with a fatty acid may be more effective [14]. Trials show that phytosterol esters of plant fatty acids obtained from canola oil, when incorporated into food such as margarine or mayonnaise, lower total cholesterol and LDL-cholesterol levels by about 10 and 15 percent, respectively [15, 16]. U.S. Pat. No. 5,502,045 (Miettinen et al., issued Mar. 26, 1996) discloses the use of sitostanol esters of canola oil to lower serum cholesterol. Benecol™(Raisio Benecol Ltd., Raisio, Finland), a margarine that contains such compounds, is now on the market.
The mechanism by which phytosterols or phytosterol esters inhibit absorption of dietary cholesterol by the digestive tract is not fully understood but may involve competitive inhibition of cholesterol uptake from the intestinal lumen or inhibition of cholesterol esterification in the intestinal mucosa [12]. It is known that phytosterols themselves are only poorly absorbed. Vanhanen et al. [17] report that phytosterol esters may also be poorly absorbed by the intestinal tract based on postprandial measurements of β-sitostanol in plasma. A direct measure of phytosterol ester uptake by the digestive tract has not been reported.
When phytosterols are esterified with fatty acids from plant sources such as canola, the long-chain polyunsaturated fatty acids (LCPUFAs) that are incorporated are predominantly of the omega-6 series. Omega-6 fatty acids do not affect plasma triglycerides. Research to date on fatty acid esters of sterols has focused only on the efficacy of the sterol in lowering cholesterol.